Characterization of PKCI and Comparative Studies with FHIT, Related Members of the HIT Protein Family

Klein, Michael G.; Yao, Yao; Slosberg, Eric D.; Lima, Christopher D.; Doki, Yuichiro; Weinstein, I. Bernard

doi:10.1006/excr.1998.4153

Cited by 65 publications

(77 citation statements)

References 23 publications

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“…Atlas Human Cancer 1.2 K filters (Clontech, Palo Alto, CA), each containing 1174 genes (for information about genes, see www.clontech.com) were used. The total RNA (3 to 4 g) was converted into cDNA and labeled with 33 PdATP using Clontech cDNA array labeling kit. Hybridizations and washes were performed following the recommended manufacturer protocol with minor modifications.…”

Section: Cdna Array Hybridizationmentioning

confidence: 99%

“…In vivo studies suggest that the ubiquitously expressed PKCI protein does not function as an inhibitor of PKC but rather acts as an enzyme in a yet to be identified pathway. 33 BENE belongs to the MAL family, which is widely expressed in various tissues, suggesting a common role of these proteins in cell biology. 34 MCM4, a DNA-replication-initiation factor, is an essential component of a protein complex that prevents DNA from being replicated more than once per cell cycle.…”

Section: Genes With Other Functionsmentioning

confidence: 99%

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Expression profiling of gastric adenocarcinoma using cDNA array

et al. 2001

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To investigate the expression profile of gastric adenocarcinoma, cDNA array experiments were performed using Atlas Human Cancer 1.2 K Array (Clontech Laboratories, Palo Alto, CA) on nine xenografted and two primary gastric cancer samples. The expression of the tumor samples was compared to that of two normal gastric epithelial tissues. The expression pattern of the primary tumors was similar to that of xenografted tumors. The up-regulated genes had expression ratios ranging from 2.5 to 16, whereas the down-regulated genes had a range from ؊2.5 to ؊16. No variation in gene expression was detected in the analysis of the xenografted tumors versus the primary tumors, indicating that the xenografts represented the primary tumors well. Thirtyeight genes showed altered gene expression in 5 or more samples (>45%). Thirty-one genes were up-regulated and seven genes were down-regulated. The most abundantly upregulated genes (ratio >5) included genes such as S100A4, CDK4, MMP14 and beta catenin. The GIF was markedly downregulated (ratio < ؊10). To confirm our findings, six genes (three up-and three down-regulated) were selected for semiquantitative RT-PCR analysis. The RT-PCR results were consistent with the array findings. Our approach revealed that several genes are abnormally expressed in gastric cancer and found that genes known to interact in several common molecular pathway(s) were consistently altered. © 2001 Wiley-Liss, Inc. Key words: cDNA arrays; gene expression; xenografts; and gastric adenocarcinomasGastric carcinoma (GC) is one of the most common malignancies worldwide and is the second most common cause of cancerrelated death. 1 Overall relative 5-year survival rates are currently less than 20%. Cytogenetic studies of gastric adenocarcinomas are few in number and have failed to identify any consistent or noteworthy chromosomal abnormalities. 2 Comprehensive studies of DNA copy number changes using comparative genomic hybridization (CGH) have revealed alterations in several chromosomal regions. 3-5 Frequent high-level amplifications were noted at 17q and 20q, whereas DNA copy number losses were frequently seen in 4q, 5q, and 9p. However, there are few data on gene expression in gastric cancer. The recent development of cDNA array technology allows the study of gene expression level and gene activation in thousands of genes and sequences. 6,7 The data obtained from the array analysis are expected to uncover novel genes related to cancer development and its clinical behavior. However, tumor sample contamination with normal cells makes analysis of hundreds of genes more difficult and less sensitive. Xenografting of human tumors has been used to produce optimal samples that are enriched for neoplastic cells for subsequent molecular analyses.

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Section: Cdna Array Hybridizationmentioning

confidence: 99%

Section: Genes With Other Functionsmentioning

confidence: 99%

Expression profiling of gastric adenocarcinoma using cDNA array

et al. 2001

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“…A human cDNA that encodes the protein HINT1 (gi:47834342) was originally isolated in our laboratory using the yeast two-hybrid system during studies designed to isolate proteins that interact with the regulatory domain of protein kinase C b (Klein et al, 1998). The encoded 13.7 kDa protein was initially named PKCI-1, for protein kinase C interacting protein-1.…”

Section: Introductionmentioning

confidence: 99%

“…Since our discovery of HINT1 by its interaction with PKC in the yeast two-hybrid system (Klein et al, 1998), other investigators have obtained evidence that HINT1 can also interact with other proteins, including the protein ATDC, which is thought to be involved in DNA repair (Brzoska et al, 1995), the protein CDK7, which plays a role in the general apparatus of transcription (Korsisaari and Makela, 2000), and MITF, a specific bHLH-zip transcription factor (Razin et al, 1999). The latter studies are of particular interest since they indicated that Ap 4 A could modulate the transcriptional activity of MITF in mast cells (Razin et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Hint1 is a haplo-insufficient tumor suppressor in mice

et al. 2005

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The HINT1 protein, a member of the histidine triad (HIT) family, is highly conserved in diverse species and ubiquitously expressed in mammalian tissues. However, its precise function in mammalian cells is not known. As a result of its structural similarity to the tumor-suppressor protein FHIT, we used homozygous-deleted Hint1 mice to study its role in tumorigenesis. We discovered that after 2 to 3 years of age the spontaneous tumor incidence in Hint1 À/À mice was significantly greater than that in wildtype Hint1 þ / þ mice (Po0.05). Using a well-established mouse model of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis we found a marked and significant (Po0.05) increase in the incidence of mammary and ovarian tumors in both, Hint1 À/À and þ /À mice versus þ / þ mice. The Hint1 À/À and þ /À mice had similar tumor incidence and similar tumor histologies. Therefore, deletion of Hint1 in mice enhances both spontaneous tumor development and susceptibility to tumor induction by DMBA. In addition, since the Hint1 þ /À tumors retained expression of the unmutated wildtype allele, Hint1 is haplo-insufficient with respect to tumor suppression in this model system.

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“…Previous studies have verified that the histidine triad nucleotide‐binding protein 1 (HINT1) is also distributed throughout the limbic system (Baumann & Bogerts, 1999; Liu, Puche, & Wang, 2008), and HINT1 belongs to the histidine triad protein super family, which possesses a conserved binding sequence motif HisXHisXHis (X = hydrophobic amino acid) (Klein et al., 1998). HINT1 was first recognized as the protein kinase C inhibitor‐1 (PKCI‐1) (Dang, Liu, Chen, Guo, & Wang, 2014).…”

Section: Introductionmentioning

confidence: 99%

Effects of Hint1 deficiency on emotional‐like behaviors in mice under chronic immobilization stress

Sun

Liu

et al. 2017

Brain and Behavior

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BackgroundHistidine triad nucleotide‐binding protein 1 (HINT1) is regarded as a haplo‐insufficient tumor suppressor and is closely associated with diverse neuropsychiatric diseases. Moreover, HINT1 is related to gender‐specific acute behavior changes in schizophrenia and in response to nicotine. Stress has a range of molecular effects in emotional disorders, which can cause a reduction in brain‐derived neurotrophic factor (BDNF) expression in the hippocampus, resulting in hippocampal atrophy and neuronal cell loss.MethodsThis study examined the role of HINT1 deficiency in anxiety‐related and depression‐like behaviors and BDNF expression in the hippocampus under chronic immobilization stress, and investigated whether the sex‐specific and haplo‐insufficient effects exist in emotional‐like behaviors under the same condition.ResultsIn a battery of behavior tests, the results of the control group, not exposed to stress, showed that knockout (KO) and heterozygosity (HT) of Hint1 had anxiolytic‐like and antidepression‐like effects on the male and female mice. However, both male and female Hint1‐KO mice showed elevated anxiety‐related and antidepression‐like behavior under chronic immobilization stress; moreover, both male and female Hint1‐HT mice displayed elevated anxiety‐related behavior and increased depression‐like behavior under chronic immobilization stress. There were no significant differences in general locomotor activity between Hint1‐KO and ‐HT mice and their wild‐type (WT) littermates. Hint1‐KO mice under basal and chronic immobilization stress conditions expressed more BDNF in the hippocampus than did Hint1‐HT and WT mice; overall, there were no significant sex differences in emotional‐like behaviors of Hint1‐KO and ‐HT mice. Additionally, Hint1‐HT mice showed haplo‐insufficient effects on emotional‐like behaviors under basic conditions, rather than under chronic immobilization stress.ConclusionsBoth male and female HINT 1 KO and HT mice had a trend of anxiolytic‐like behavior and antidepression‐like behavior at control group. However, both male and female HINT1 KO mice showed elevated anxiety‐related and antidepression‐like behavior under chronic immobilization stress; moreover, both male and female HINT1 HT mice displayed elevated anxiety‐related behavior and increased depression‐like behavior under chronic immobilization stress.

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Characterization of PKCI and Comparative Studies with FHIT, Related Members of the HIT Protein Family

Cited by 65 publications

References 23 publications

Expression profiling of gastric adenocarcinoma using cDNA array

Expression profiling of gastric adenocarcinoma using cDNA array

Hint1 is a haplo-insufficient tumor suppressor in mice

Effects of Hint1 deficiency on emotional‐like behaviors in mice under chronic immobilization stress

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